Six separate projects related to outcomes of patients with rheumatic diseases are included in this report. The first project, Genetic determinants of ankylosing spondylitis severity, is a prospective observational study of 800 subjects with ankylosing spondylitis (AS) that seeks to identify genetic determinants of ankylosing spondylitis severity. The severity of AS varies widely among patients, but the reasons for this variation are unknown. Because the susceptibility to AS is largely genetically determined, it is possible that the severity of AS may also be largely genetically determined. This project will test genotype-phenotype correlations in a large sample, stratified by duration of AS to capture inflammatory signs in early duration subjects and the degree of fusion and functional impairment in late duration subjects. Over 800 subjects have been enrolled, and genetic testing and data analysis has begun. Radiographic data and HLA data have been finalized on 702 patients. Recent findings have included the identification of immunogenetic markers associated with more severe spinal fusion, the finding that hip arthritis has larger impact on physical functioning than spinal damage, and characterization of the typical pattern of radiographic involvment of different joint areas. Collaborators include Drs. J. Reveille, M. Weisman, J. Davis, T. Learch, and J. Malley. In a related genome wide association study, we identified ARTS1, IL23R, and IL1R as associated with the susceptibility to AS, along with areas on 2 chromosomes not known to contain genes. We will next test associations of these markers with measures of functional and radiographic severity, and will similarly test associations with several candidate genes involved in bone formation and regulation. The second project, Progression of spinal fusion in ankylosing spondylitis, is a feasibility study with a goal to develop and test a measure of spinal fusion in AS based on quantification of calcification of the lumbar intervertebral discs by computed tomography. Thirty-one subjects have been enrolled, and 23 have completed follow-up scans at 1 and 2 years. We have extended this study to include follow-up radiographs at 4 years, and have included a second arm to test the short-term reliability of measurements. Collaborators on this project are Drs. J. Flynn, L. Yao, Y. Yao, S. Tan, and R. Summers. The third project, Clinically important changes in rheumatoid arthritis, is a prospective observational study of clinically important changes in rheumatoid arthritis (RA) activity. Current criteria for improvement in RA have not emphasized the patients perspective. It is also not known if patients rate changes in their symptoms and signs of RA similarly as their physicians, or if different patients are concordant in their judgments of how much of an improvement in symptoms represents an important improvement. The goals of this project are to identify benchmarks of important improvement in pain, functioning, and global arthritis status in RA based on the self-assessment by patients of changes in their symptoms. A secondary goal is to examine the measurement properties of preference measures. To date, 178 patients have been assessed before and after escalation of their anti-rheumatic treatment. In an initial study, we found that a new method of measuring patient global asessment, using a rating scale with marker states, was no more valid than the traditionally used visual analog scale. The fourth project, Measurement of physical functioning, uses secondary analysis of clinical trial and observational data to understand what aspects of functioning are being measured in commonly used self-report instruments. One focus is to study the relationship between measures of physical performance and measures of self-reported functional limitations. We have developed and tested a model of this relationship using data from NHANES III, annd found that performance measures are neither sensitive nor specific indicators of self-reported functional limitations. We have also found that, contrary to much previous literature, women and men have similar levels of self-reported functional limitations. The difference between our results and previous literature likely resulted because we performed more extensive adjustment for potential confounding factors. The fifth project, Malignancy in patients with rheumatoid arthritis, uses the Medicare-SEER database to compare the incidence and survival from cancer between patients with RA and those without RA. Rheumatoid arthritis may modify the risk of malignancy, increasing the risk of certain types of cancer (lymphoma, lung) and decreasing the risk of other types of cancer (colorectal). However, risks of malignancy are not well defined in patients with RA, nor is it known if the outcomes of cancer are similar between patients with RA and those without RA. The Medicare-SEER database is a large population-based linked database that combines clinical information from Medicare billing records with cancer data from SEER locations. SEER is the nation's primary cancer epidemiology program, operated by the National Cancer Institute. Patients with RA are identified from Medicare records, while cancer incidence is obtained from SEER. Data analysis is currently underway. The goals of the sixth project, Clinical epidemiology of systemic lupus erythematosus, are to better estimate the prevalence of systemic lupus erythematosus (SLE), to investigate health disparities among patients with SLE, and to identify clinical features and health care practices that are associated with mortality. Administrative data have been used to identify socioeconomic differences in the incidence of end-stage renal disease due to lupus nephritis, and are planning further studies to examine if these differences are related to access to care. We are beginning a study of quality of care indicators for hospitalized patients with systemic lupus erythematosus.